tetano
Editor, Senior Moderator
Immunity
. 2020 Oct 20;S1074-7613(20)30447-7.
doi: 10.1016/j.immuni.2020.10.006. Online ahead of print.
Unbiased Screens Show CD8 [SUP]+[/SUP] T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein
Andrew P Ferretti[SUP] 1 [/SUP], Tomasz Kula[SUP] 1 [/SUP], Yifan Wang[SUP] 1 [/SUP], Dalena M V Nguyen[SUP] 1 [/SUP], Adam Weinheimer[SUP] 1 [/SUP], Garrett S Dunlap[SUP] 1 [/SUP], Qikai Xu[SUP] 1 [/SUP], Nancy Nabilsi[SUP] 1 [/SUP], Candace R Perullo[SUP] 1 [/SUP], Alexander W Cristofaro[SUP] 1 [/SUP], Holly J Whitton[SUP] 1 [/SUP], Amy Virbasius[SUP] 1 [/SUP], Kenneth J Olivier Jr[SUP] 1 [/SUP], Lyndsey R Buckner[SUP] 2 [/SUP], Angela T Alistar[SUP] 3 [/SUP], Eric D Whitman[SUP] 3 [/SUP], Sarah A Bertino[SUP] 1 [/SUP], Shrikanta Chattopadhyay[SUP] 1 [/SUP], Gavin MacBeath[SUP] 4 [/SUP]
Affiliations
Abstract
Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8[SUP]+[/SUP] T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8[SUP]+[/SUP] T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8[SUP]+[/SUP] T cell immunity to SARS-CoV-2.
Keywords: CD8+ T cells; COVID-19; SARS-CoV-2; T-Scan; immunity; immunodominant epitopes; novel coronavirus; seasonal coronaviruses; spike protein; vaccine.
. 2020 Oct 20;S1074-7613(20)30447-7.
doi: 10.1016/j.immuni.2020.10.006. Online ahead of print.
Unbiased Screens Show CD8 [SUP]+[/SUP] T Cells of COVID-19 Patients Recognize Shared Epitopes in SARS-CoV-2 that Largely Reside outside the Spike Protein
Andrew P Ferretti[SUP] 1 [/SUP], Tomasz Kula[SUP] 1 [/SUP], Yifan Wang[SUP] 1 [/SUP], Dalena M V Nguyen[SUP] 1 [/SUP], Adam Weinheimer[SUP] 1 [/SUP], Garrett S Dunlap[SUP] 1 [/SUP], Qikai Xu[SUP] 1 [/SUP], Nancy Nabilsi[SUP] 1 [/SUP], Candace R Perullo[SUP] 1 [/SUP], Alexander W Cristofaro[SUP] 1 [/SUP], Holly J Whitton[SUP] 1 [/SUP], Amy Virbasius[SUP] 1 [/SUP], Kenneth J Olivier Jr[SUP] 1 [/SUP], Lyndsey R Buckner[SUP] 2 [/SUP], Angela T Alistar[SUP] 3 [/SUP], Eric D Whitman[SUP] 3 [/SUP], Sarah A Bertino[SUP] 1 [/SUP], Shrikanta Chattopadhyay[SUP] 1 [/SUP], Gavin MacBeath[SUP] 4 [/SUP]
Affiliations
- PMID: 33128877
- PMCID: PMC7574860
- DOI: 10.1016/j.immuni.2020.10.006
Abstract
Developing effective strategies to prevent or treat coronavirus disease 2019 (COVID-19) requires understanding the natural immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used an unbiased, genome-wide screening technology to determine the precise peptide sequences in SARS-CoV-2 that are recognized by the memory CD8[SUP]+[/SUP] T cells of COVID-19 patients. In total, we identified 3-8 epitopes for each of the 6 most prevalent human leukocyte antigen (HLA) types. These epitopes were broadly shared across patients and located in regions of the virus that are not subject to mutational variation. Notably, only 3 of the 29 shared epitopes were located in the spike protein, whereas most epitopes were located in ORF1ab or the nucleocapsid protein. We also found that CD8[SUP]+[/SUP] T cells generally do not cross-react with epitopes in the four seasonal coronaviruses that cause the common cold. Overall, these findings can inform development of next-generation vaccines that better recapitulate natural CD8[SUP]+[/SUP] T cell immunity to SARS-CoV-2.
Keywords: CD8+ T cells; COVID-19; SARS-CoV-2; T-Scan; immunity; immunodominant epitopes; novel coronavirus; seasonal coronaviruses; spike protein; vaccine.